Early Changes in Lymphocyte Counts Predict Clinical Outcomes in Hepatocellular Carcinoma Treated With Durvalumab Plus...

Durvalumab plus tremelimumab (Dur/Tre) has shown promising efficacy in advanced hepatocellular carcinoma (HCC), but predictive biomarkers remain unclear. This study aimed to determine whether early changes in peripheral blood lymphocyte counts during Dur/Tre therapy can predict clinical outcomes.

In this multicenter retrospective study, we evaluated 299 patients with advanced HCC to assess whether early changes in peripheral blood lymphocyte counts predict clinical outcomes during Dur/Tre therapy. Changes in lymphocyte counts at 2 weeks after treatment initiation (2w-Δlymphocyte) were analyzed in relation to objective response rate (ORR), progression-free survival (PFS), and overall survival.

Patients with a high-2w-Δlymphocyte (> +107/μL) demonstrated a significantly higher ORR (29.6% vs. 14.0%, p < 0.001) and longer PFS (4.3 vs. 2.8 months, p = 0.035) compared with those with a low-2w-Δlymphocyte (≤ +107/μL). Subgroup analyses showed that higher 2w-Δlymphocyte values were associated with better PFS across modified albumin-bilirubin grades (p = 0.011), Barcelona Clinic Liver Cancer stages (p = 0.007), and baseline lymphocyte-to-monocyte ratio (p < 0.001).

Early increases in peripheral blood lymphocyte counts, particularly 2w-Δlymphocyte, may be associated with treatment response to Dur/Tre and provide complementary dynamic information to established prognostic factors. Although a favorable association with PFS was observed, this association was attenuated after propensity score matching. Further prospective studies are warranted to validate the clinical utility of 2w-Δlymphocyte.